A minimally invasive assay for individual assessment of the ATM/CHEK2/p53 pathway activity

Kabacik, Sylwia; Ortega-Molina, Ana; Efeyan, Alejo; Finnon, Paul; Bouffler, Simon; Serrano, Manuel; Badie, Christophe

doi:10.4161/cc.10.7.15231

Cited by 29 publications

(23 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studying gene transcription in human cells after radiation exposure provides a molecular approach for assessing radiation doses (55), detecting inter-individual differences in response (56) and aiding assessment of long-term risks (57). Indeed, transcription is much more complex than simply the production of transcripts of protein-coding genes and a number of miRNAs have been identified which target DDR components, e.g., miR-100, miR-101 and miR-421 down-regulate ATM expression (58-60), miR-125b and miR-504 directly regulate TP53 expression (61, 62) and miR-605 and miR-661 target the MDM2 gene (63,64).…”

Section: Discussionmentioning

confidence: 99%

Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

et al. 2015

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

et al. 2015

View full text Add to dashboard Cite

“…Finally, inherited ATM mutations are also felt to play a role in familial pancreatic ductal adenocarcinoma (32)(33)(34). Radiosensitivity and chemosensitivity and ATM Radiosensitivity is also a hallmark of the A-T syndrome (35,36). Increased toxicity to radiotherapy has been reported in patients with A-T syndrome and heterozygous carriers of ATM mutations, probably due to defective DNA repair and genomic instability in normal tissues (37)(38)(39)(40).…”

Section: Germ-line Atm Heterozygosity and Cancer Susceptibilitymentioning

confidence: 99%

“…As referenced above, heterozygous germ-line ATM mutations appear to impart some vulnerability to chemotherapy and radiotherapy toxicity. To this end, many groups have designed assays to measure ATM protein function (36,54,63,64).…”

Section: Somatic Atm Mutations In Cancermentioning

confidence: 99%

ATM Mutations in Cancer: Therapeutic Implications

Choi¹,

Kipps²,

Kurzrock³

2016

Molecular Cancer Therapeutics

390

318

View full text Add to dashboard Cite

Activation of checkpoint arrest and homologous DNA repair are necessary for maintenance of genomic integrity during DNA replication. Germ-line mutations of the ataxia telangiectasia mutated (ATM) gene result in the well-characterized ataxia telangiectasia syndrome, which manifests with an increased cancer predisposition, including a 20% to 30% lifetime risk of lymphoid, gastric, breast, central nervous system, skin, and other cancers. Somatic ATM mutations or deletions are commonly found in lymphoid malignancies, as well as a variety of solid tumors. Such mutations may result in chemotherapy resistance and adverse prognosis, but may also be exploited by existing or emerging targeted therapies that produce synthetic lethal states.

show abstract

“…Interestingly, such effects induced by radiation are similar to those induced by senescence in CFU-S13 (Figures 3 and 4, Supplemental Figure 1), suggesting that radiation accelerates aging. Previous reports indicated that the radiation-dose-dependent activation of the ATM/Chek2/p53 pathway, which is related to DNA damage and repair, 24 and the suppression of the PI3K/AKT pathway, which is related to cell proliferation, 25 occur simultaneously 4 weeks after 0.6-and 3-Gy whole-body irradiation, as shown by microarray analysis (Supplemental Figure 2), 26,27 suggesting that apoptotic signals operate in young mice. Accordingly, although the number of peripheral blood cells in irradiated mice did not change compared with that in the nonirradiated controls, the cell cycle of HPCs following irradiation appeared to be accelerated simultaneously with somewhat impaired, i.e., ineffective hematopoiesis in young mice.…”

Section: Discussionmentioning

confidence: 93%

Cell cycle of primitive hematopoietic progenitors decelerated in senescent mice is reactively accelerated after 2-Gy whole-body irradiation

Hirabayashi

Tsuboi

Kuramoto

et al. 2016

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Aging is considered to be a functional retardation of continuous xenobiotic responses over a lifetime after the developmental period; thus, the effects of ionizing radiation over a lifetime may be somewhat accounted for by a modifier of aging effects. This study was conducted to evaluate the possible/synergic effects of radiation during aging by determining cell-cycle parameters of hematopoietic stem cells/hematopoietic progenitor cells (HSCs/HPCs), such as the percent of cells in cycling, the generation doubling time, and the cumulative cycling-cell fraction, by bromodeoxyuridine-ultraviolet assay, which enables the determination of their cycling capacity in vivo. Colony-forming progenitor cells, such as colony-forming unit (CFU)-granulocyte/macrophage (GM), CFU in the spleen on day 9 (CFU-S9), and CFU-S on day 13 (CFU-S13) for mature, less mature, and immature HPCs, respectively, were evaluated in young and old mice (6 weeks and 21 months of age, respectively) with or without 2-Gy whole-body irradiation and a 4-week recovery period. Then, cell-cycle parameters were evaluated and compared. As a result, the generation doubling time of all types of HPC was prolonged by the irradiation in both young and old mouse groups, except that of CFU-S13 in old mice, which showed acceleration of the cell cycle following the irradiation. In addition, only CFU-S13 in irradiated old mice showed a significant increase in the cumulative cycling-cell-fraction ratio. Significant changes due to the effects of aging and irradiation on HPCs were observed only in the immature HPCs, i.e., the cell cycle of immature HPCs was suppressed by aging without irradiation and was, in contrast, accelerated as the cells recovered from radiation-induced damage. This suggests that the mechanisms of peripheral blood recovery after 2-Gy whole-body irradiation are markedly different between young and old mice, although 21-month-old mice showed almost the same level of recovery as the young mice.

show abstract

A minimally invasive assay for individual assessment of the ATM/CHEK2/p53 pathway activity

Cited by 29 publications

References 52 publications

Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

ATM Mutations in Cancer: Therapeutic Implications

Cell cycle of primitive hematopoietic progenitors decelerated in senescent mice is reactively accelerated after 2-Gy whole-body irradiation

Contact Info

Product

Resources

About